Event Details

Background

One-carbon metabolism is a crucial network of pathways involved in cellular methylation reactions and nucleotide biosynthesis. The network is regulated by and dependent on several micronutrients. Of these, folate (Vitamin B9) and vitamin B12 play central roles as cofactors in the network. In the last two decades, folic acid fortification policies and voluntary supplementation have increased folic acid intake. The cumulative folic acid intake from fortification, supplementation, diet and other sources can easily exceed the upper limit set forth for folic acid (1000 μg/day). Some observational studies suggest an interaction between elevated folate/folic acid levels and vitamin B12 metabolism, raising the concern that high folate/folic acid status may exacerbate biomarkers of vitamin B12 deficiency and cognitive decline in older adults taking multivitamin supplements. Another growing concern is the appearance of unmetabolized folic acid in nearly all serum samples from US populations, as seen in the NHANES screening program. The biological activity or longtime health implications of higher unmetabolized folic acid exposures are not clear. The biological premise and experimental evidence for establishing a causal effect for the consequences of elevated folic acid intake and the role of high folate status in modifying the effects of vitamin B12 deficiency are lacking, and most animal and in vitro studies aimed at addressing this issue have suffered from experimental study design limitations. Research consensus on the approaches to investigate folate/folic acid -vitamin B12 interactions are urgently needed to assess the safety aspects associated with potential excess intake of folic acid.

Objectives

Main objectives of the workshop are to deliberate on the potential causal mechanisms of excess folate/folic acid and Vit B12 deficiency, as well as potential biological effects of unmetabolized folic acid and to develop consensus on various basic and clinical experimental study designs, intervention strategies and experimental models, for exploring the biochemical mechanisms for these interactions.

Observational studies suggest that folic acid may possess idiosyncratic functions not ascribed to the more physiological forms of folate (other than its role in the DHFR saturation): what are those functions, at what exposure levels of folic acid does this occur, and what are the at-risk groups?

Observational data suggests that an excess of folate exposure, regardless of its form, has adverse effects on B12 status: at what exposure levels does this occur, are there plausible biological mechanisms, and what are the at-risk groups?

Observational studies also suggest that an excess of folate exposure, regardless of the form ingested, may have adverse effects in addition to the concern raised in query #2. At what exposure levels do these adverse effects occur, what are the plausible biological mechanisms, and what are the at-risk groups?

What are the biological effects and health implications of free folic acid?
Chairs: Jean-Louis Gueant, University of Lorraine and INSERM
Richard Finnell, Baylor College of Medicine

What types of dose-response data are needed, including biological and physiological endpoints, to better understand the requirements and risks of excess folate?
Chairs: Regan Bailey, Purdue University
Yvonne Lamers, University of British Columbia

What types of dose-response data are needed, including the biological and physiological endpoints, to better understand the interactions between folate excess in B12 deficiency?
Chairs: David Rosenblatt, McGill University Health Centre
Barry Shane, University of California, Davis

10:30 a.m. – 11:00 a.m.

Break

11:00 a.m. – 12:00 p.m.

Breakout Session Reports

12:00 p.m. – 12:30 p.m.

Consensus - Building on the Research Strategies and Discussing Next Steps
Joel Mason, Tufts University
Patrick Stover, Texas A&M University